Symptomatic therapy of irritable bowel syndrome with colonic spasms and distension.

Posology

Adults including the elderly
1 – 2 capsules (equivalent to 0.2 - 0.4 mL peppermint oil) three times daily.

Paediatric population

Adolescents aged 12 to 17 years:
1 capsule (equivalent to 0.2 mL peppermint oil) three times daily.

Children aged 8 to 11 years:
1 capsule (equivalent to 0.2 mL peppermint oil) two times daily.

Children under 8 years of age:
Colpermin is contraindicated in children under 8 years of age because of safety concerns (see section 4.3).

Special population
No data are available for a dosing instruction in case of impaired renal function.

Duration of use
Colpermin gastro–resistant hard capsules should be taken until symptoms resolve, usually within one or two weeks.
 
At times when the symptoms are more persistent, the intake of Colpermin gastro– resistant hard capsules can be continued for periods of no longer than 3 months per course.

Method of administration
The capsules should be swallowed whole with some liquid at least 30 minutes before or after meals.
They must not be chewed, crushed or broken before swallowing, see section 4.4. If one or more doses have been missed, the next dose is to be taken as usual.
The capsule should be carefully removed from the blister.

Hypersensitivity to peppermint oil, menthol or of any ingredient, see section 6.1. Hypersensitivity to arachis oil (peanut oil) or soya. Colpermin capsules contain arachis oil (peanut oil), and should not be taken by patients known to be allergic to peanut. As there is a possible relationship between allergy to peanut and allergy to soya, patients with soya allergy must also avoid Colpermin. Patients with liver disease, cholangitis, achlorhydria, gallstones and any other biliary disorders. Children under 8 years of age due to the presence of pulegone and menthofuran in peppermint oil and the lack of clinical data in this age group.

The capsules should be swallowed whole, i.e., not broken or chewed, because this would release the peppermint oil prematurely, possibly causing local irritation of the mouth and oesophagus.

Treatment should be discontinued in patients suffering from heartburn or hiatal hernia as they sometimes have an exacerbation of these symptoms after taking peppermint oil.

No interaction studies have been performed.

Use of food or antacids administered at the same time could cause early release of capsule content which could cause gastrointestinal irritation or reduce efficacy.
Other medicinal products used to reduce stomach acid, such as histamine-2 blockers, proton pump inhibitors or antacids may cause premature dissolution of the enteric coating. Therefore Colpermin should be taken at least 2 hours before or after the intake of food, antacids or other medicines used to reduce stomach acid.

Pregnancy

 
There are limited to no amount of data regarding the use of peppermint oil in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Colpermin is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breastfeeding
Data suggests excretion of peppermint constituents / metabolites in human milk.A risk to the newborns/infants cannot be excluded. Colpermin should not be used during breastfeeding.

Fertility
There are no available data on the effects of peppermint oil on fertility.

Colpermin has no or negligible influence on the ability to drive and use machines. However, no studies on the effect on the ability to drive and use machines have been performed.

 

a)      Summary of the safety profile

 

Hypersensitivity to menthol was reported, with headache, bradycardia, tremor, ataxia, anaphylactic shock, erythematous rash and pruritus. The frequency is not known.

In such cases, Colpermin must be discontinued immediately.

 

b)      Tabulated list of adverse reactions of Colpermin

 

Included are undesirable effects reported in the studies mentioned below as well as from spontaneous reporting or literature. Their frequency of occurrence is not known, since the events were reported from a population of an unknown size.

 

The following definitions apply to the incidence of undesirable effects:

Very Common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very Rare (< 1/10,000); Not Known (cannot be estimated from the available data).

 

Common undesirable effects of Colpermin include pyrosis, anorectal discomfort, headache, abnormal smell of faeces, dry mouth, nausea, and vomiting.

 

Adverse drug reactions by frequency and system organ class (SOC)

 

 

SOC	Frequency	Reaction
Immune system disorders	Uncommon	Hypersensitivity.
	Not known	Anaphylactic shock.
Nervous system disorders	Common	Headache.
	Not known	Tremor, ataxia.
Eye disorders	Uncommon	Blurred vision.

 

Cardiac disorders	Not known	Bradycardia.
Gastrointestinal disorders	Common	Pyrosis, nausea, vomiting, anorectal discomfort, dry mouth, abnormal smell of feces.
	Uncommon	Gastric haemorrhage.
	Not known	Perianal pain, diarrhoea.
Skin and subcutaneous tissue disorders	Uncommon	Pruritus.
	Not known	Erythematous rash.
Renal and urinary disorders	Not known	Dysuria, inflammation of the glans of the penis, urine odour abnormal.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the herbal medicinal product is important. It allows continued monitoring of the benefit/risk balance of the herbal medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

 

•          To report any side effect(s):

 

§  Saudi Arabia:

 

•          The National Pharmacovigilance and Drug Safety Centre (NPC) •          SFDA Call Center: 19999 •          E-mail: npc.drug@sfda.gov.sa •          Website: www.sfda.gov.sa/npc

 

 

§  Other GCC States:

•          Please contact the relevant competent authority.

 

 

Symptoms
Overdose may cause severe gastro-intestinal symptoms, diarrhoea, rectal ulceration, epileptic convulsions, loss of consciousness, apnoea, nausea, and disturbances in cardiac rhythms, ataxia and other CNS problems, probably due to the presence of menthol.

Management
In the event of overdose, the stomach should be emptied by gastric lavage. Observation should be carried out with symptomatic treatment, if necessary.

Pharmacotherapeutic group: Other drugs for functional gastrointestinal disorders, ATC code: A03AX15.
Mechanism of action: Colpermin has a relaxant and antispasmodic effect on the intestinal muscles in intestinal overexcitability, particularly in case of irritable bowel syndrome. Colpermin gastro resistant hard capsules prevent irritation of the stomach, through which the capsules pass undissolved. Menthol (from peppermint oil) is released within about 20 minutes but not until the alkaline environment of the intestine, where it acts as a local intestinal agent, particularly in the colon.

Pharmacodynamics: Peppermint oil exerts a local, dose-dependent muscle relaxant effect and thus results in a reduction of intestinal wall tension. The effect is due to an interaction between menthol and voltage-dependent calcium channels.

Clinical efficacy: The clinical efficacy of Colpermin was studied in eight studies involving 404 patients with irritable bowel syndrome. Five double-blind, controlled studies were placebo-controlled, in two studies a comparison with a spasmolytic drug was used, and in one study a stress management programme was used in the control group. Of the five placebo-controlled studies, four achieved a statistically significant result in favour of peppermint oil. In a controlled study in 42 children improvements were reported in 71% of the patients receiving Colpermin compared with 43% receiving placebo after a two-week treatment (𝑥2 [6, n=42] = 9.5, p<0.002).

Absorption: After ingestion of peppermint oil (Colpermin), the active substance menthol reaches the small and large sections of the intestine unchanged. The active substance is released continuously from the hydrophobic paste formulation. The absorption of peppermint was measured in 13 healthy subjects on the basis of the renal elimination of the main component, menthol. After administration of three Colpermin capsules a mean absorption of 39% was calculated. The lag-time was 1.07 hours and a Tmax of 5 hours was determined.

Distribution: No distribution studies are available.

Metabolism: Menthol, as the main ingredient of peppermint oil, is eliminated predominantly as the glucuronide. Animal studies have shown that menthol is also excreted in the form of the sulphate.

Elimination: The elimination of peppermint oil was measured in 13 healthy subjects on the basis of the renal elimination of the main component, menthol. After administration of three Colpermin capsules, 95.5 mg menthol (as the glucuronide) was eliminated in the urine over a 24-hour period.

Kinetics of special patient groups: The kinetics of special patient groups (e.g. in patients with hepatic or renal insufficiency, genetic polymorphism) have not been studied.

Preclinical data concerning repeated dose toxicity are insufficient and therefore of limited informative value. Based on the long standing clinical use there is a sufficiently established safety of the usage of peppermint oil in the given posology (up to 1.2 mL daily) in humans.

A standard battery of genotoxicity studies (in vitro bacterial reverse mutation assay, in- vitro mouse lymphoma assay, in vivo bone marrow micronucleus assay) showed that Colpermin peppermint oil has no genotoxic potential.

The highest recommended daily dose is 1.2 mL peppermint oil, i.e., 1.122 mg peppermint oil, which contains a maximum of 37.03 mg pulegone + menthofuran. For a person weighing 50 kg this would correspond to a daily intake of 0.74 mg/kg bw. No cases of liver damage caused by peppermint oil or mint oil were reported under that posology.

Tests on reproductive toxicity and carcinogenicity have not been performed.

Capsule content:   

 -    Beeswax, white
-    Arachis oil, refined
-    Silica, colloidal anhydrous

Capsule wall:  

 -    Gelatine
-    Indigotine (E132)
-    Titanium dioxide (E171)
-    Methacrylic acid-methyl methacrylate copolymer (1:2)
-    Methacrylic acid-ethyl acrylate copolymer (1:1)
-    Triethyl citrate
-    Glycerol monostearate 40-55
-    Macrogol 4000
-    Talc.

None.

3 years

Do not store above 25 °C. Store in the original container.

Colpermin is available in PVC/aluminium blister strips, each containing ten capsules. The blister strips are packed in cartons containing 20 capsules (2 strips).

There are no special requirements for disposal. The capsules should be carefully removed from the blister.